Title Promoter Affiliations Abstract "Fetal repair of gastroschisis and other innovations in fetal surgery" "Jan Deprest" "Urogenital, Abdominal and Plastic Surgery" "To investigate the safety and efficacy of fetal repair of gastroschisis, as well as other innovations in fetal surgery, such as prenatal bladder derivation and surgical closure of the fetal membranes." "Single Orifice and Robotic Solutions for Fetal Surgery" "Elisenda Eixarch Roca, Jan Deprest" "Urogenital, Abdominal and Plastic Surgery, Robotics, Automation and Mechatronics (RAM)" "Around 1% of the babies are born with a severe birth defect each year and collectively these defects are estimated to be responsible for over 1/3 of all paediatric hospital admissions. Studies have shown that surgeries performed before birth have better long-term effects on the babies as compared to the surgeries performed after birth. However open womb surgery is an extreme option for fetal surgery which may induce severe side effects on both the fetus and the mother. The purpose of this PhD is to explore the possibilities of robotics solutions in single orifice minimally invasive fetal surgery. Minimally invasive fetal surgery is safer than open womb surgery but the current surgical tools and techniques are not suitable for the unique environment of the womb. This PhD will not only work to improve the current tools and methods utilized by the surgeons but also endeavour to bring technical innovation." "The development of novel tools for fetal surgery in spina bifida aperta: a translational and clinical investigation" "Anna David, Jan Deprest" "Urogenital, Abdominal and Plastic Surgery" "We will explore the potential of in-house developed innovations in the field of fetal imaging, image-guided procedures and minimally invasive fetal surgery for spina bifida. These innovations include an anti-adhesive patch, ultrasound-guiding system, neural stem cells, and a patient-empowered medical multicenter perinatal database." "ARTISTE - Autonomous Robotic Suturing for fetal surgery" "Emmanuel Vander Poorten" "Robotics, Automation and Mechatronics (RAM)" "Single-Port Access surgery (SPA) demonstrates significant potential as an alternative to traditional multi-port Minimally Invasive Surgery (MIS). In contrast to conventional MIS, SPA employs a single incision or a natural orifice to reach the surgical site. SPA is particularly well-suited for treating Open Spina Bifida (OSB), which necessitates strict limitations on port diameter (10 mm O.D.). In OSB repair, suturing is widely regarded as the most demanding and time-intensive task. The ARTISTE project endeavors to address this highly challenging task by using KUL's macro-micro robotic system, along with the application of artificial intelligence (AI) and augmented reality (AR) techniques. The project will commence by exploring multi-sensor fusion to ensure reliable and accurate multi-arm instrument proprioception, followed by path planning and AR/VR visualization for in-utero suturing. Ultimately, the project aims to demonstrate the autonomous suturing capabilities of the macro-micro system under environmental contact. If receiving approval from ethical committee, the autonomous suturing demonstration will be carried out in collaboration with the clinical partner on two or three pregnant sheep." "Impact of the bacterial colonic metabolism on fecal water toxicity as biomarkers of future colorectal cancer risk after bariatric surgery" "Kristin Verbeke" "Translational Research in GastroIntestinal Disorders, Clinical and Experimental Endocrinology" "Bariatric surgery is an effective way to treat obesity. Roux-en-Y gastric bypass (RYGB) reduces the gastric volume and bypasses parts of the small intestine so that malabsorption is induced whereasSleeve Gastrectomy (SG) only reduces the volume of the stomach without inducing malabsorption. Although bariatric surgery reduces overall cancer risk, evidence indicates that the risk for colorectal cancer (CRC) is increased and might depend on the type of surgery. We hypothesize that bariatric surgery modifies the bacterial colonic environment which contributes to the future CRC risk. A one-year follow-up study will be conducted in obese patients undergoing bariatric surgery and a control group of obese patients on a weight loss diet. Blood and fecal samples will be collected prior to and at specific time points after surgery or weight loss diet. We will characterize the colonic fermentation by analyzing metabolite profiles of the fecal samples, the composition of the microbiota and the bile acid composition and compare their capacity to induce toxicity in cultured colonic cells. Also the contribution of inflammation to toxicity will be taken into account. With multivariate statistical methods, we will identify those parameters that are associated with increased toxicity." "The role of fetal brain magnetic resonance imaging in current fetal medicine" "Steven Dymarkowski" "Translational MRI, Woman and Child, Urogenital, Abdominal and Plastic Surgery" "Fetal MRI has become an important adjunct to prenatal ultrasound in the assessment of fetal abnormalities, and certainly so abnormalities of the central nervous system. Although initially perceived as competing modalities  it has become clear that both modalities should complement each other where indicated, permitting better understanding of the disease process, classification of abnormalities, and determination of prognosis and management options. Over the last decades several in utero treatment options have been proven beneficial and effective, including laser coagulation in complicated monochorionic pregnancies, in utero closure of spina bifida aperta and most recently fetoscopic endoluminal tracheal occlusion (FETO) in congenital diaphragmatic hernia.Because of the efficacy of fetal surgery for spina bifida aperta, accurate prenatal imaging of fetuses with spina bifida aperta has become a need to select fetuses eligible for fetal surgery. In chapter 4 we demonstrated the reliability of MRI in measuring the posterior fossa dimensions as well as the changes in these within 7 days after fetal surgery. In Chapter 5 we described the range and prevalence of supratentorial anomalies on MRI in fetuses with open spina bifida eligible for fetal surgery (Chapter 5). Despite the availability of ultrafast sequences, fetal motion is limiting the image quality. With the use of post-processing techniques it is now possible to create motion-free 3D image volumes compared to the acquired image stacks with lower resolution. In chapter 6 the post-processing and segmentation of these volume allowed us to demonstrate differences in the fetal brain volume and shape of fetuses with open spina bifida before and after fetal surgery, in comparison to normal controls. Several fetal MRI atlases  of fetuses with normal fetal brain development are available, yet brain development in fetuses with open spina bifida is altered, first because of the defect and again that course may change after fetal surgery. In chapter 7 we developed a spatio-temporal atlas based on fetal MRI volumes demonstrating the pre- and postoperative brain development in fetuses with open spina bifida.Another target group of fetal surgery candidates are  selected fetuses with congenital diaphragmatic hernia. Because infants with CDH are known to be at risk for significant neurodevelopmental delay, we wanted to investigate if those fetuses would have already in utero altered brain development when compared to normal controls. We found a significant difference in brain development at 28 weeks of gestation, which is the time point fetal surgery typically is offered. (chapter 8).Fetuses infected with cytomegalovirus (CMV) in the first pregnancy are also known to be at risk of neurodevelopmental delay. However the relation between prenatal brain abnormalities on imaging, and later neurocognitive impairment remain incompletely understood. In chapter 9 we demonstrated there is a correlation between the grading performed on ultrasound and fetal MRI, but the latter imaging method is more performing. Furthermore, we found significant differences on diffusion weighted imaging in several brain regions of  CMV-infected fetuses compared to non-CMV-infected fetuses.Monochorionic diamniotic pregnancies complicated by twin-to-twin-transfusion syndrome (TTTS) are preferentially treated with laser coagulation of the anastomoses; in selected cases fetal reduction by cord occlusion may be chosen. Because fetuses from a complicated MC twin pregnancy are at increased risk of antenatal brain lesions, we routinely offer third trimester MRI to fetuses having undergone surgery. The prevalence of brain lesions detected by fetal MRI turned out to be higher compared to prenatal ultrasound alone (Chapter 10). Therefore, fetal MRI in the third trimester seems to be a useful adjunct after in utero surgery for TTTS." "Improving management techniques in conditions affecting the fetal brain" "Luc De Catte" "Urogenital, Abdominal and Plastic Surgery, Woman and Child" "This project will include research into the most recent developments in prenatal therapies concerning the fetal central nervous system. Especially focused on three different subjects: - Fetal cytomegalovirus infections: current status of the screening protocol in Belgium and its need for adjustment. The role of MRI in diagnostics. The possibility of Vanciclovir as treatment of first trimester CMV infections. This study is part of a long-term study on the neurological outcome of children with congenital CMV. - Spina Bifida and fetal surgery: Parent's choices in prenatal therapies. A new method for evaluating the outcome of the currently existing surgical methods prenatally. - Vein of Galen malformations: first steps towards intrauterine coiling" "Reducing invasiveness of fetal spina bifida repair - Towards novel techniques." "Jan Deprest" "Urogenital, Abdominal and Plastic Surgery" "Though not a lethal condition, the prenatal correction of open spina bifida aperta (SBA) was proposed, because it could halt its in utero progressive nature hence prevent severe postnatal morbidity. In 1995, fetal surgery was proven safe and effective in the fetal lamb model. After initial exploratory clinical trials demonstrating feasibility and safety, in 2011 the randomized clinical trial (Management Of Myelomeningocele Study, MOMS) demonstrated the efficacy of midgestational anatomical SBA fetal repair. Prenatal, rather than postnatal repair, reduces the brain shunt rate at 12 months, increases the likelihood of walking at 30 months and reduces intermittent catheterization rates at school age. This comes at the expense of an increased risk for prematurity and maternal morbidity, both in the index and subsequent pregnancies. The hysterotomy, through which the procedure is done, is responsible in subsequent pregnancies for a 10% risk of rupture with concomitant fetal death in nearly one in two cases. To reduce these side effects, the concept of fetoscopic SBA repair was reintroduced. Though theoretically attractive, we thought we could not embrace it clinically without proper preclinical validation.We first conducted a systematic review in chapter 4 showing that in fetal lambs, a two-layer SBA repair through hysterotomy is safe and effective. However, functional assessment methods were lacking in this model, and the lesion was induced in different ways and used to study either the effects on the spinal cord or the brain. In chapter 5, we showed that motor evoked potentials recording and analysis in neonatal lambs is feasible and can reliably assess neuromotor function. Furthermore in chapter 6 we demonstrated that prenatal myelotomy replicates the full phenotype of a lumbar myeloschisis. We eventually reported in chapter 7 that a layered watertight compared to non-watertight fetal repair achieves in this model more neuroprotection and better brain and spinal cord neuromorphology.In preparation for clinical implementation, we investigated whether such watertight repair could be done by fetoscopy. In chapter 8 a systematic review of the clinical literature indicated that, in its early experience, fetoscopy was not safe yet neuroprotective. One factor explaining lack of safety was the use of CO2 for amnio-insufflation, which in lambs induces fetal acidosis and hypercapnia. We therefore assessed the feasibility and safety of fetoscopic repair using humidified and heated CO2. In chapter 9, we showed this was feasible and safe using an anesthetic technique that maintains maternal physiological homeostasis.In parallel, we performed in chapter 10 a meta-analysis to determine the learning curve of open and fetoscopic approaches and assess the need for training. Surgeons reach competency after 35 cases for standard hysterotomy. For percutaneous fetoscopy, competency is not reached prior to 56 cases. We then designed a five-step training program for fetoscopic SBA repair on a pelvic trainer, rabbit cadavers, a high-fidelity model in rabbits, fetal lambs and finally human fetuses. We trained three fetal surgeons and showed in chapter 11 that ≥33 procedures may be necessary to reach competency. Eventually, our fetal team successfully performed three human fetoscopic SBA repair and propose to implement this training program more broadly." "Impact of Fetal Growth Restriction on lung development (Fetal Lung)" "Jan Deprest" "Urogenital, Abdominal and Plastic Surgery" "Rationale The term fetal growth restriction (FGR) refers to those fetuses failing to achieve their full growth potential during prenatal life. When this condition occurs, the risk of intrauterine demise is 5-to 10-fold higher compared with normally growing fetuses. This status becomes particularly relevant since it affects 7-10% of all pregnancies. Furthermore, growth restricted fetuses have worse perinatal outcomes and are at higher risk of long-term complications than the general population. It is well established that both genetic predisposition and environmental influence are two main contributors to the establishment of disease. However, it has been reported that insults occurring in specific critical periods of fetal development may lead to impaired physical and/or functional outcomes both in early and later life. Thus, some individuals might be born with increased susceptibility to present certain disorders depending on when, where and for how long the adverse event had taken place. The attractiveness of all this is that, if correctly identified, these episodes could provide an opportunity for intervention aiming to either eliminate or reduce its negative impact on the fetus. Our objective is to prospectively characterize lung structure and function in different cohorts of individuals who had FGR and controls at distinct stages of human development (fetus, child, adolescent, adult). Hypotheses Our main hypothesis is that FGR has a detrimental effect on fetal lung development that persists after birth and that could also be responsible for postnatal impaired pulmonary functional capacity and respiratory morbidity. Our specific hypotheses are: - FGR has a negative impact on the development of the fetal lung. - The negative impact of FGR on lung development persists in postnatal life in the form of impaired pulmonary functional capacity. - Adults who suffered FGR are more likely to develop lung disease both in the structural and functional facets. - The addition of other stress factors, such as smoking, to the condition of FGR advances the deterioration of the lung function. Objectives Our main objective is to characterize lung development and function across life course in FGR using imaging techniques, pulmonary function tests and blood biomarkers. Our specific objectives are as follows: - To characterize fetal lung development in FGR using imaging techniques (US and MRI) and cord blood biomarkers. - To evaluate pulmonary function in children and adolescents who experienced FGR by means of pulmonary function tests. - To assess pulmonary structure and function among adults with FGR with imaging techniques (CT), pulmonary function testing and blood biomarkers. - To describe the effect of additional stress factors, such as smoking, on the lung characteristics and performance of adult individuals who had been FGR." "Novel fetal management strategies of gastroschisis and urinary tract obstruction" "Jan Deprest" "Urogenital, Abdominal and Plastic Surgery" "Fetal surgery has become a reality, and the introduction of minimally invasive techniques broadens potentially the scope of conditions. In urinary tract obstruction the main obstacles are (non-invasive) assessment of deterioration of renal function and technical limitations to explore the bladder neck at the time of in utero surgery. Gastroschisis can technically also be covered, though formal assessment of the benefits must still take place."